Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadjage/sex = 1.3 [95%CI 0.9–1.8]; Padjage/sex 0.14) compared to individuals with the genotype GG (ORadjage/sex = 0.77 [95%CI 0.56–1.0]; Padjage/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadjage/sex = 0.77 [95%CI 0.5–1.1]; Padjage/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (ORadjage = 1.3 [95% CI = 0.9–2.0]; Padjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0–1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadjage = 1.4 [1.1–1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadjage/sex = 2.0 [95%CI 0.83–5.0]; Padjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0–4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.

Background: Leishmaniasis is an infectious disease caused by Leishmania parasites. A Th1 immune response is necessary in the acute phase to control the pathogen. The triggering receptor expressed on myeloid cells (TREM)-1 is a potent amplifier of inflammation. Our aim is to identify whether the TREM1 variant rs2234237 A/T (Thr25Ser) is associated with the disease development of cutaneous leishmaniasis (CL) in Leishmania guyanensis-infected individuals. The effects of the rs2234237 genotypes on plasma cytokines IL-1β, IL-6, IL-8, IL-10, MCP-1 and TNF-α are also investigated. Methods: 838 patients with CL and 818 healthy controls (HCs) living in the same endemic areas were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Plasma cytokines were assayed in 400 patients with CL and 400 HCs using the BioPlex assay. Results: The genotypes’ and alleles’ frequencies were similar in both patients with CL (AA = 618, 74%; AT = 202, 24%; TT = 18, 2%) and in HCs (AA = 580, 71%; AT = 220, 27%; TT = 18, 2%). Rs2234237 showed a modest effect on plasma IL-10 that disappeared when correction of the p-value was applied. Plasma IL-10 by rs2234237 genotypes were (mean ± SEM; AA = 2.91 pg/mL ± 0.14; AT = 2.35 pg/mL ± 0.12; TT = 3.14 pg/mL ± 0.56; p = 0.05). Conclusion: The TREM1 rs2234237 (Thr25Ser) seems to have no influence on the susceptibility or resistance to L. guyanensis infections.